Anti-methicillin-resistant Staphylococcus aureus assay of azalomycin F_(5a) and its derivatives  

作　　者：YUAN Gan-Jun LI Pei-Bo YANG Jun PANG Hui-Zhong PEI Ying 

机构地区：[1]College of Bioscience and Engineering, Jiangxi Agricultural University [2]School of Life Science,Sun Yat-sen University

出　　处：《Chinese Journal of Natural Medicines》2014年第4期309-313,共5页中国天然药物（英文版）

基　　金：supported by the Jiangxi Province Science and Technology Supporting Plan(No.20111BBG7006-1);the National Natural Science Foundation of China(No.81260476)

摘　　要：AIM: To discover anti-methicillin-resistant Staphylococcus aureus(anti-MRSA) microbial natural products or their derivatives. METHOD: Azalomycin F5a(1) was prepared through fermentation of Streptomyces hygroscopicus var. azalomyceticus, and its derivatives were synthesized through hydrocarbylation in hydrocarbyl alcoholic-AcOH(4 : 1) and subsequent demalonylation with 2 mol·L-1 KOH in MeOH-H2O(7 : 3). Their activities against MRSA ATCC 33592 and three clinical MRSA isolates were evaluated by the agar diffusion and broth microdilution methods. RESULTS: Four demalonylazalomycin F5a derivatives 2 to 5 were synthesized. The anti-MRSA activity assay indicated that compounds 1 to 5 showed remarkable activity against MRSA, and their minimum inhibitory concentrations(MICs) were respectively 3.0-4.0, 0.5-1.0, 0.67-1.0, 0.67-0.83, and 0.5-0.83 μg·mL-1. CONCLUSION: Azalomycin F5a and the demalonylazalomycin F5a derivatives 2-5 showed remarkable anti-MRSA activity, and the anti-MRSA activities of 2 to 5 were higher than that of 1, while the anti-MRSA activities of 2 to 5 showed no obvious differences. It was also shown that the malonyl monoester group of azalomycin F5a was less important for its anti-MRSA activity.AIM： To discover anti-methicillin-resistant Staphylococcus aureus （anti-MRSA） microbial natural products or their derivatives. METHOD： Azalomycin F5a （1） was prepared through fermentation of Streptomyces hygroscopicus var. azalomyceticus, and its derivatives were synthesized through hydrocarbylation in hydrocarbyl alcoholic？AcOH （4 ： 1） and subsequent demalonylation with 2 mol·L^-1 KOH in MeOH？H2O （7 ： 3）. Their activities against MRSA ATCC 33592 and three clinical MRSA isolates were evaluated by the agar diffusion and broth microdilution methods. RESULTS： Four demalonylazalomycin F5a derivatives 2 to 5 were synthesized. The anti-MRSA activity assay indicated that compounds 1 to 5 showed remarkable activity against MRSA, and their minimum inhibitory concentrations （MICs） were respectively 3.0？4.0, 0.5？1.0, 0.67？1.0, 0.67？0.83, and 0.5？0.83 μg·mL^-1. CONCLUSION： Azalomycin F5a and the demalonylazalomycin F5a derivatives 2？5 showed remarkable anti-MRSA activity, and the anti-MRSA activities of 2 to 5 were higher than that of 1, while the anti-MRSA activities of 2 to 5 showed no obvious differences. It was also shown that the malonyl monoester group of azalomycin F5a was less important for its anti-MRSA activity.

关 键 词：Azalomycin F5a ANTI-MRSA Demalonyl Derivatives Macrocyclic antibiotics 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]